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Binding of DCC by Netrin-1 to Mediate Axon Guidance Independent of Adenosine A2B Receptor Activation

Science  09 Mar 2001:
Vol. 291, Issue 5510, pp. 1976-1982
DOI: 10.1126/science.1059391

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Abstract

Netrins stimulate and orient axon growth through a mechanism requiring receptors of the DCC family. It has been unclear, however, whether DCC proteins are involved directly in signaling or are mere accessory proteins in a receptor complex. Further, although netrins bind cells expressing DCC, direct binding to DCC has not been demonstrated. Here we show that netrin-1 binds DCC and that the DCC cytoplasmic domain fused to a heterologous receptor ectodomain can mediate guidance through a mechanism involving derepression of cytoplasmic domain multimerization. Activation of the adenosine A2B receptor, proposed to contribute to netrin effects on axons, is not required for rat commissural axon outgrowth or Xenopusspinal axon attraction to netrin-1. Thus, DCC plays a central role in netrin signaling of axon growth and guidance independent of A2B receptor activation.

  • * Present address: Department of Neurobiology, Pharmacology and Physiology, University of Chicago, J. F. Knapp Research Center, Room 216, 924 East 57 Street, Chicago, IL 60637, USA.

  • To whom correspondence should be addressed. E-mail: marctl{at}itsa.ucsf.edu

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